Chemotherapy-Induced Febrile NeutropeniaNCT04000711
Safety and Efficacy of Ambulatory Versus In-hospital Antibiotic Treatment in Children With Febrile Neutropenia
A study testing Outpatient oral treatment. and Inpatient intravenous treatment. in people with Chemotherapy-Induced Febrile Neutropenia, run by Hospital Infantil de Mexico Federico Gomez.
Trial summary
Febrile neutropenia (FN) continues to be the infectious complication that most commonly requires hospitalization in pediatric cancer patients undergoing chemotherapy. In recent years, data have been published on the effectiveness of treatment of FN events with oral antibiotics, mainly in developed countries, but data… Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Chemotherapy-Induced Febrile Neutropenia
- What is being tested?
- Outpatient oral treatment. and Inpatient intravenous treatment.
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2015to 8 Oct 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children from 1 to 18 years of age.
- Underlying cancer diagnosis that presented with fever and neutropenia secondary to chemotherapy and after 48-72 hours of inpatient intravenous treatment with Cefepime, were hemodynamically stable, remained afebrile for at least 24 hours, and did not have a documented source of infection.
- Participants whose caretaker knew how to read and write and accepted to be part of the clinical trial.
Who cannot join
- Participants with positive cultures.
- Absolute neutrophil count (ANC) < 100/mm3.
- Thrombocytopenia < 30,000/mm3.
- Less than 7 days have passed from the start of the last chemotherapy session.
- Leukemia on remission induction therapy.
- Relapsed leukemia.
Show all 11Show fewer
- Mucositis grade III or IV.
- Participants with allergy to cefixime.
- Need to receive any other medication intravenously.
- Need of oxygen support, parenteral nutrition or intravenous fluids.
- Oral intolerance.
About this study
Official title: Safety and Efficacy of Ambulatory Versus In-hospital Antibiotic Treatment in Pediatric Patients With Cancer and Febrile Neutropenia: a Non-inferiority Multicenter Randomized Clinical Trial
Febrile neutropenia (FN) continues to be the infectious complication that most commonly requires hospitalization in pediatric cancer patients undergoing chemotherapy. In recent years, data have been published on the effectiveness of treatment of FN events with oral antibiotics, mainly in developed countries, but data from developing countries continue to be scarce.
Our hypothesis was that early change from initial in-patient intravenous antibiotic treatment to oral outpatient antibiotic treatment in children with cancer and FN is as safe and effective as in-patient intravenous antibiotic management.
Read more
The purpose of this clinical study was to determine whether early outpatient oral antibiotic treatment is not inferior in safety and efficacy to in-hospital intravenous antibiotic treatment in pediatric patients with cancer and low-risk FN events.
A multicenter, non-inferiority randomized clinical trial was conducted in three public hospitals in Mexico City. Low-risk FN events were identified in children aged 1 to 18 years. After 48 to 72 hours of receiving intravenous in-hospital antibiotics, children were randomly allocated to receive outpatient oral treatment (cefixime) or to continue in-hospital intravenous treatment (cefepime). Daily monitoring was performed until the resolution of neutropenia. Our outcome of interest was the presence of any unfavorable clinical outcome.
Read the detailed description
Introduction: Febrile neutropenia (FN) continues to be the infectious complication that most commonly requires hospitalization in pediatric cancer patients undergoing chemotherapy. Classically these patients have been managed as inpatient. In recent years, data have been published on the effectiveness of treatment of FN events with oral antibiotics, mainly in developed countries, but data from developing countries continue to be scarce.
Hypothesis: Our hypothesis was that early change from initial in-patient intravenous antibiotic treatment to oral outpatient antibiotic treatment in children with cancer and FN is as safe and effective as in-patient intravenous antibiotic management.
Objectives: The purpose of this clinical study was to determine whether early outpatient oral antibiotic treatment is not inferior in safety and efficacy to in-hospital intravenous antibiotic treatment in pediatric patients with cancer and low-risk FN events.
Methodology: A multicenter, non-inferiority randomized clinical trial was conducted in three public hospitals in Mexico City. Low-risk FN events were identified in children aged 1 to 18 years.
A complete medical history, physical examination and review of laboratory tests and cultures were performed on all subjects with FN events who were considered low risk. According to local guidelines for the treatment of FN, all subjects began receiving cefepime at a dose of 150 mg/kg/day. Subjects were followed-up daily, and those who met the inclusion/exclusion criteria after 48 to 72 hours of in-hospital intravenous treatment with cefepime were randomly assigned to receive outpatient treatment with oral cefixime at a dose of 8 mg/kg/day or to continue in-hospital intravenous treatment. The treatment was administered by the researchers.
Participants in both treatment groups were evaluated daily by a complete physical examination. Subjects in the outpatient group were evaluated at the outpatient clinic of the hospital. All patients underwent a blood count every 48 to 72 hours. FN event resolution was defined as when the patient remained afebrile and the absolute neutrophil count (ANC) increased to above 500 per microliter. If fever resumed, the antibiotic regimen was modified. If the subjects were in the outpatient group, they were re-admitted to the hospital to receive intravenous antibiotics. Resolution of the FN event was defined as the end of participation of the subjects in the study, and they were followed up for an additional 72 hours.
The occurrence of any of the following conditions was considered an unfavorable clinical outcome: 1) therapeutic failure, defined as the resumption of fever in a patient with persistent neutropenia. For all patients with resumption of fever, the antibiotic regimen was switched, and if the patients were in the outpatient treatment group, they were re-admitted to the hospital; 2) new focus of infection, documented both by the clinical condition and by laboratory and other diagnostic tests; 3) hemodynamic instability, defined as a decrease in blood pressure below the 5th percentile for the patient age that did not revert with the administration of crystalloid solutions; and 4) death.
Sample size: The sample size was calculated to reject a null hypothesis of inferiority, with a non-inferiority margin of presentation of unfavorable clinical outcomes of 15%. A formula including a statistical power of 80% and a one-tailed alpha value of 0.025 was used to calculate the sample size of 2 independent proportions. Based on previous reports of 10% of unfavorable clinical outcomes during the management of FN events, the calculation yielded a total of 63 FN events per group for a total of 126 events.
Randomization: A random sequence balanced by blocks of 4 FN events was generated using a computer program. A physician who did not participate in the subject selection assigned subjects to receive either outpatient oral treatment at home or to continue in-hospital intravenous treatment. If the subjects lived more than 1 hour away from the hospital, they were assigned to a care home to ensure that they could return to the hospital in case of any event. Because the study intervention involved outpatient treatment, the study was open. All patients were provided with the antibiotic free of charge.
Statistical analysis: The focus of analysis was intention-to-treat. For each comparison group, measures of central tendency and dispersion were estimated for continuous variables, and absolute and relative frequencies were determined for discrete and nominal variables. The statistical test performed to test the hypothesis of non-inferiority is very similar to the traditional test for comparison of proportions; the only difference is that the non-inferiority margin is added to the formula, and a p-value < 0.05 confirms non-inferiority. The statistical program STATA version 14.2 was used for the analysis.
- Conditions
- Chemotherapy-Induced Febrile Neutropenia
- Being tested
- Outpatient oral treatment., Inpatient intravenous treatment.
- Keywords
- Fever and neutropenia, Febrile neutropenia, Cancer, Outpatient treatment, Children
- Medical subject headings
- Chemotherapy-Induced Febrile Neutropenia, Fever, Neutropenia, Febrile Neutropenia, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Outpatient oral treatment.Other
Participants allocated in oral outpatient group were discharged home with oral antibiotic to continue management. Participants were given Cefixime oral suspension (100 mg/5 mL). Antibiotic was given to the caretakers with written instructions about dosage and time of administration. Dosage indicated was 8 mg/kg/day to be given orally as a single dose (max dose 400 mg/day). Oral antibiotic treatment was given until documented ANC > 500, failure to treatment (restart of fever) or when 14 days of antibiotic were completed (whichever occurred first).
Inpatient intravenous treatment.Other
Participants allocated in the intravenous inpatient group continued receiving Cefepime 150 mg/kg/day every 8 hours (max dose 2 grams per dose or 6 grams per day) according to local standard of care guidelines. Intravenous antibiotic treatment was given until documented ANC > 500, failure to treatment (restart of fever) or when 14 days of antibiotic were completed (whichever occurred first).
| Study group | Role | What they receive |
|---|---|---|
| Outpatient oral antibiotic treatment group. | Experimental | After randomization, participants assigned to receive outpatient treatment with oral cefixime at a dose of 8 mg/kg/day were discharged. Treatment was provided by the researchers. Subjects were evaluated daily at the outpatient clinic of the hospital. All patients underwent a blood count every 48 to 72 hours. FN event resolution was defined as when the patient remained afebrile and the ANC increased to above 500 per microliter. If fever resumed in the outpatient group, they were re-admitted to the hospital to receive intravenous antibiotics. Resolution of the FN event was defined as the end of participation of the subjects in the study, and they were followed up for an additional 72 hours. Receives: Other: Outpatient oral treatment. |
| Inpatient intravenous antibiotic treatment group. | Active comparator | After randomization, participants continued intravenous inpatient antibiotic with cefepime 150 mg/kg/day according to local standard of care guidelines. Subjects were evaluated daily. All patients underwent a blood count every 48 to 72 hours. FN event resolution was defined as when the patient remained afebrile and the ANC increased to above 500 per microliter. If fever resumed, treatment was changed according to clinical guidelines. Resolution of the FN event was defined as the end of participation of the subjects in the study, and they were followed up for an additional 72 hours. Receives: Other: Inpatient intravenous treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Therapeutic failure as unfavorable clinical outcome of children with fever and neutropenia treated with oral outpatient antibiotic.
Occurrence of therapeutic failure, defined as the resumption of fever in a patient with persistent neutropenia. For all patients with resumption of fever, the antibiotic regimen was switched, and if the patients were in the outpatient treatment group, they were re-admitted to the hospital.
Measured: 17 days after randomization.
New focus of infection as unfavorable clinical outcome of children with fever and neutropenia treated with oral outpatient antibiotic.
Presence of a new focus of infection, documented both by the clinical condition and by laboratory and other diagnostic tests.
Measured: 17 days after randomization.
Hemodynamic instability as unfavorable clinical outcome of children with fever and neutropenia treated with oral outpatient antibiotic.
Presence of hemodynamic instability, defined as a decrease in blood pressure below the 5th percentile for the patient age that did not revert with the administration of crystalloid solutions.
Measured: 17 days after randomization.
Secondary outcomes (1)
Presentation of any adverse reaction to any given antibiotic (oral or intravenous) of children with fever and neutropenia treated with oral outpatient vs intravenous inpatient management.
Moderate and severe adverse reaction to antibiotics given, described as an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product, which predicts hazard from future administration and warrants prevention or specific treatment, or alteration of the dosage regimen, or withdrawal of the product.
Measured: Started on the day of enrollment and concluded 17 days after.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2019
- Study start1 Jul 2015
- Primary completion30 Sep 2017
- Study completion8 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Chemotherapy-Induced Febrile NeutropeniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A multicenter, noninferiority randomized clinical trial was conducted in three public hospitals in Mexico City. A complete medical history, physical examination and review of laboratory tests and cultures were performed on all subjects with FN events who were considered low risk. All subjects began receiving intravenous inpatient treatment with cefepime. Subjects were followed-up daily, and those who met the inclusion/exclusion criteria after 48 to 72 hours of in-hospital intravenous treatment were randomly assigned to receive outpatient treatment with oral cefixime or to continue in-hospital intravenous treatment. The treatment was administered by the researchers.
- Masking
- None (open label)
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Infantil de Mexico Federico Gomez
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto Nacional de Pediatria, Hospital Juarez de Mexico
- Responsible party
- Principal investigator, Martha Josefina Avilés Robles, Hospital Infantil de Mexico Federico Gomez
- Investigators
- Martha J. Aviles Robles, Principal investigator, Hospital Infantil de Mexico Federico Gomez
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04000711
- Sponsor's protocol ID
- HIM-2014-026
- Other IDs
- 233555
- Status last verified
- Jun 2019
- First submitted
- 24 Jun 2019
- Last updated
- 27 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR; Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011 Feb 15;52(4):e56-93. doi: 10.1093/cid/cir073.
PubMed 21258094Santolaya ME, Rabagliati R, Bidart T, Paya E, Guzman AM, Morales R, Braun S, Bronfman L, Ferres M, Flores C, Garcia P, Letelier LM, Puga B, Salgado C, Thompson L, Tordecilla J, Zubieta M; Sociedad Chilena de Infectologia; Sociedad Chilena de Hematologia. [Consensus: Rational approach towards the patient with cancer, fever and neutropenia]. Rev Chilena Infectol. 2005;22 Suppl 2:S79-113. Epub 2005 Nov 4. Spanish.
PubMed 16311689Lehrnbecher T, Phillips R, Alexander S, Alvaro F, Carlesse F, Fisher B, Hakim H, Santolaya M, Castagnola E, Davis BL, Dupuis LL, Gibson F, Groll AH, Gaur A, Gupta A, Kebudi R, Petrilli S, Steinbach WJ, Villarroel M, Zaoutis T, Sung L; International Pediatric Fever and Neutropenia Guideline Panel. Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation. J Clin Oncol. 2012 Dec 10;30(35):4427-38. doi: 10.1200/JCO.2012.42.7161. Epub 2012 Sep 17.
PubMed 22987086Santolaya ME, Alvarez AM, Aviles CL, Becker A, Cofre J, Enriquez N, O'Ryan M, Paya E, Salgado C, Silva P, Tordecilla J, Varas M, Villarroel M, Viviani T, Zubieta M. Prospective evaluation of a model of prediction of invasive bacterial infection risk among children with cancer, fever, and neutropenia. Clin Infect Dis. 2002 Sep 15;35(6):678-83. doi: 10.1086/342064. Epub 2002 Aug 23.
PubMed 12203164Hakim H, Flynn PM, Srivastava DK, Knapp KM, Li C, Okuma J, Gaur AH. Risk prediction in pediatric cancer patients with fever and neutropenia. Pediatr Infect Dis J. 2010 Jan;29(1):53-9. doi: 10.1097/INF.0b013e3181c3f6f0.
PubMed 19996816Vidal L, Ben Dor I, Paul M, Eliakim-Raz N, Pokroy E, Soares-Weiser K, Leibovici L. Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients. Cochrane Database Syst Rev. 2013 Oct 9;2013(10):CD003992. doi: 10.1002/14651858.CD003992.pub3.
PubMed 24105485Zapata-Tarrés Marta, Klünder-Klünder Miguel, Cicero-Oneto Carlo, Rivera-Luna Roberto, Ortega-Ríos Velasco Fernando, Cortés Gallo Gabriel et al . Análisis de la atención de las complicaciones durante el tratamiento de niños con leucemia linfoblástica aguda. Bol. Med. Hosp. Infant. Mex.
Aviles-Robles M, Ojha RP, Gonzalez M, Ojeda-Diezbarroso K, Dorantes-Acosta E, Jackson BE, Johnson KM, Caniza MA. Bloodstream infections and inpatient length of stay among pediatric cancer patients with febrile neutropenia in Mexico City. Am J Infect Control. 2014 Nov;42(11):1235-7. doi: 10.1016/j.ajic.2014.07.021. Epub 2014 Sep 16.
PubMed 25234044Aviles-Robles MJ, Reyes-Lopez A, Otero-Mendoza FJ, Valencia-Garin AU, Penaloza-Gonzalez JG, Rosales-Uribe RE, Munoz-Hernandez O, Garduno-Espinosa J, Juarez-Villegas L, Zapata-Tarres M. Safety and efficacy of step-down to oral outpatient treatment versus inpatient antimicrobial treatment in pediatric cancer patients with febrile neutropenia: A noninferiority multicenter randomized clinical trial. Pediatr Blood Cancer. 2020 Jun;67(6):e28251. doi: 10.1002/pbc.28251. Epub 2020 Mar 20.
PubMed 32196898
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Ambulatory Versus In-hospital Antibiotic Treatment in Pediatric Patients With Cancer and Febrile Neutropenia: a Non-inferiority Multicenter Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04000711
- Acronym / sponsor ID
- HIM-2014-026
- Conditions
- Chemotherapy-Induced Febrile Neutropenia
- Keywords
- Fever and neutropenia, Febrile neutropenia, Cancer, Outpatient treatment, Children
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 117 participants (actual)
- Lead sponsor
- Hospital Infantil de Mexico Federico GomezUniversity, hospital or other
- Collaborators
- Instituto Nacional de Pediatria, Hospital Juarez de Mexico
- Study start
- 1 Jul 2015 (actual)
- Primary completion
- 30 Sep 2017 (actual)
- Study completion
- 8 Oct 2017 (actual)
- First posted
- 27 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Febrile neutropenia (FN) continues to be the infectious complication that most commonly requires hospitalization in pediatric cancer patients undergoing chemotherapy. In recent years, data have been published on the effectiveness of treatment of FN events with oral antibiotics, mainly in developed countries, but data from developing countries continue to be scarce.
Our hypothesis was that early change from initial in-patient intravenous antibiotic treatment to oral outpatient antibiotic treatment in children with cancer and FN is as safe and effective as in-patient intravenous antibiotic management.
The purpose of this clinical study was to determine whether early outpatient oral antibiotic treatment is not inferior in safety and efficacy to in-hospital intravenous antibiotic treatment in pediatric patients with cancer and low-risk FN events.
A multicenter, non-inferiority randomized clinical trial was conducted in three public hospitals in Mexico City. Low-risk FN events were identified in children aged 1 to 18 years. After 48 to 72 hours of receiving intravenous in-hospital antibiotics, children were randomly allocated to receive outpatient oral treatment (cefixime) or to continue in-hospital intravenous treatment (cefepime). Daily monitoring was performed until the resolution of neutropenia. Our outcome of interest was the presence of any unfavorable clinical outcome.
Detailed description
Introduction: Febrile neutropenia (FN) continues to be the infectious complication that most commonly requires hospitalization in pediatric cancer patients undergoing chemotherapy. Classically these patients have been managed as inpatient. In recent years, data have been published on the effectiveness of treatment of FN events with oral antibiotics, mainly in developed countries, but data from developing countries continue to be scarce.
Hypothesis: Our hypothesis was that early change from initial in-patient intravenous antibiotic treatment to oral outpatient antibiotic treatment in children with cancer and FN is as safe and effective as in-patient intravenous antibiotic management.
Objectives: The purpose of this clinical study was to determine whether early outpatient oral antibiotic treatment is not inferior in safety and efficacy to in-hospital intravenous antibiotic treatment in pediatric patients with cancer and low-risk FN events.
Methodology: A multicenter, non-inferiority randomized clinical trial was conducted in three public hospitals in Mexico City. Low-risk FN events were identified in children aged 1 to 18 years.
A complete medical history, physical examination and review of laboratory tests and cultures were performed on all subjects with FN events who were considered low risk. According to local guidelines for the treatment of FN, all subjects began receiving cefepime at a dose of 150 mg/kg/day. Subjects were followed-up daily, and those who met the inclusion/exclusion criteria after 48 to 72 hours of in-hospital intravenous treatment with cefepime were randomly assigned to receive outpatient treatment with oral cefixime at a dose of 8 mg/kg/day or to continue in-hospital intravenous treatment. The treatment was administered by the researchers.
Participants in both treatment groups were evaluated daily by a complete physical examination. Subjects in the outpatient group were evaluated at the outpatient clinic of the hospital. All patients underwent a blood count every 48 to 72 hours. FN event resolution was defined as when the patient remained afebrile and the absolute neutrophil count (ANC) increased to above 500 per microliter. If fever resumed, the antibiotic regimen was modified. If the subjects were in the outpatient group, they were re-admitted to the hospital to receive intravenous antibiotics. Resolution of the FN event was defined as the end of participation of the subjects in the study, and they were followed up for an additional 72 hours.
The occurrence of any of the following conditions was considered an unfavorable clinical outcome: 1) therapeutic failure, defined as the resumption of fever in a patient with persistent neutropenia. For all patients with resumption of fever, the antibiotic regimen was switched, and if the patients were in the outpatient treatment group, they were re-admitted to the hospital; 2) new focus of infection, documented both by the clinical condition and by laboratory and other diagnostic tests; 3) hemodynamic instability, defined as a decrease in blood pressure below the 5th percentile for the patient age that did not revert with the administration of crystalloid solutions; and 4) death.
Sample size: The sample size was calculated to reject a null hypothesis of inferiority, with a non-inferiority margin of presentation of unfavorable clinical outcomes of 15%. A formula including a statistical power of 80% and a one-tailed alpha value of 0.025 was used to calculate the sample size of 2 independent proportions. Based on previous reports of 10% of unfavorable clinical outcomes during the management of FN events, the calculation yielded a total of 63 FN events per group for a total of 126 events.
Randomization: A random sequence balanced by blocks of 4 FN events was generated using a computer program. A physician who did not participate in the subject selection assigned subjects to receive either outpatient oral treatment at home or to continue in-hospital intravenous treatment. If the subjects lived more than 1 hour away from the hospital, they were assigned to a care home to ensure that they could return to the hospital in case of any event. Because the study intervention involved outpatient treatment, the study was open. All patients were provided with the antibiotic free of charge.
Statistical analysis: The focus of analysis was intention-to-treat. For each comparison group, measures of central tendency and dispersion were estimated for continuous variables, and absolute and relative frequencies were determined for discrete and nominal variables. The statistical test performed to test the hypothesis of non-inferiority is very similar to the traditional test for comparison of proportions; the only difference is that the non-inferiority margin is added to the formula, and a p-value < 0.05 confirms non-inferiority. The statistical program STATA version 14.2 was used for the analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A multicenter, noninferiority randomized clinical trial was conducted in three public hospitals in Mexico City. A complete medical history, physical examination and review of laboratory tests and cultures were performed on all subjects with FN events who were considered low risk. All subjects began receiving intravenous inpatient treatment with cefepime. Subjects were followed-up daily, and those who met the inclusion/exclusion criteria after 48 to 72 hours of in-hospital intravenous treatment were randomly assigned to receive outpatient treatment with oral cefixime or to continue in-hospital intravenous treatment. The treatment was administered by the researchers.
| Arm | Type | Receives |
|---|---|---|
| Outpatient oral antibiotic treatment group. | Experimental | Other: Outpatient oral treatment.After randomization, participants assigned to receive outpatient treatment with oral cefixime at a dose of 8 mg/kg/day were discharged. Treatment was provided by the researchers. Subjects were evaluated daily at the outpatient clinic of the hospital. All patients underwent a blood count every 48 to 72 hours. FN event resolution was defined as when the patient remained afebrile and the ANC increased to above 500 per microliter. If fever resumed in the outpatient group, they were re-admitted to the hospital to receive intravenous antibiotics. Resolution of the FN event was defined as the end of participation of the subjects in the study, and they were followed up for an additional 72 hours. |
| Inpatient intravenous antibiotic treatment group. | Active comparator | Other: Inpatient intravenous treatment.After randomization, participants continued intravenous inpatient antibiotic with cefepime 150 mg/kg/day according to local standard of care guidelines. Subjects were evaluated daily. All patients underwent a blood count every 48 to 72 hours. FN event resolution was defined as when the patient remained afebrile and the ANC increased to above 500 per microliter. If fever resumed, treatment was changed according to clinical guidelines. Resolution of the FN event was defined as the end of participation of the subjects in the study, and they were followed up for an additional 72 hours. |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Children from 1 to 18 years of age.
- Underlying cancer diagnosis that presented with fever and neutropenia secondary to chemotherapy and after 48-72 hours of inpatient intravenous treatment with Cefepime, were hemodynamically stable, remained afebrile for at least 24 hours, and did not have a documented source of infection.
- Participants whose caretaker knew how to read and write and accepted to be part of the clinical trial.
Key exclusion criteria (11 listed)
- Participants with positive cultures.
- Absolute neutrophil count (ANC) < 100/mm3.
- Thrombocytopenia < 30,000/mm3.
- Less than 7 days have passed from the start of the last chemotherapy session.
- Leukemia on remission induction therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Outpatient oral treatment.Participants allocated in oral outpatient group were discharged home with oral antibiotic to continue management. Participants were given Cefixime oral suspension (100 mg/5 mL). Antibiotic was given to the caretakers with written instructions about dosage and time of administration. Dosage indicated was 8 mg/kg/day to be given orally as a single dose (max dose 400 mg/day). Oral antibiotic treatment was given until documented ANC > 500, failure to treatment (restart of fever) or when 14 days of antibiotic were completed (whichever occurred first). | Other | Outpatient oral antibiotic treatment group. |
| Inpatient intravenous treatment.Participants allocated in the intravenous inpatient group continued receiving Cefepime 150 mg/kg/day every 8 hours (max dose 2 grams per dose or 6 grams per day) according to local standard of care guidelines. Intravenous antibiotic treatment was given until documented ANC > 500, failure to treatment (restart of fever) or when 14 days of antibiotic were completed (whichever occurred first). | Other | Inpatient intravenous antibiotic treatment group. |
Primary outcome
Therapeutic failure as unfavorable clinical outcome of children with fever and neutropenia treated with oral outpatient antibiotic.
Time frame: 17 days after randomization.
Occurrence of therapeutic failure, defined as the resumption of fever in a patient with persistent neutropenia. For all patients with resumption of fever, the antibiotic regimen was switched, and if the patients were in the outpatient treatment group, they were re-admitted to the hospital.
New focus of infection as unfavorable clinical outcome of children with fever and neutropenia treated with oral outpatient antibiotic.
Time frame: 17 days after randomization.
Presence of a new focus of infection, documented both by the clinical condition and by laboratory and other diagnostic tests.
Hemodynamic instability as unfavorable clinical outcome of children with fever and neutropenia treated with oral outpatient antibiotic.
Time frame: 17 days after randomization.
Presence of hemodynamic instability, defined as a decrease in blood pressure below the 5th percentile for the patient age that did not revert with the administration of crystalloid solutions.
1 secondary outcome
Presentation of any adverse reaction to any given antibiotic (oral or intravenous) of children with fever and neutropenia treated with oral outpatient vs intravenous inpatient management.
Time frame: Started on the day of enrollment and concluded 17 days after.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2019.
- Background: PubMed 21258094Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR; Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011 Feb 15;52(4):e56-93. doi: 10.1093/cid/cir073.
- Background: PubMed 16311689Santolaya ME, Rabagliati R, Bidart T, Paya E, Guzman AM, Morales R, Braun S, Bronfman L, Ferres M, Flores C, Garcia P, Letelier LM, Puga B, Salgado C, Thompson L, Tordecilla J, Zubieta M; Sociedad Chilena de Infectologia; Sociedad Chilena de Hematologia. [Consensus: Rational approach towards the patient with cancer, fever and neutropenia]. Rev Chilena Infectol. 2005;22 Suppl 2:S79-113. Epub 2005 Nov 4. Spanish.
- Background: PubMed 22987086Lehrnbecher T, Phillips R, Alexander S, Alvaro F, Carlesse F, Fisher B, Hakim H, Santolaya M, Castagnola E, Davis BL, Dupuis LL, Gibson F, Groll AH, Gaur A, Gupta A, Kebudi R, Petrilli S, Steinbach WJ, Villarroel M, Zaoutis T, Sung L; International Pediatric Fever and Neutropenia Guideline Panel. Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation. J Clin Oncol. 2012 Dec 10;30(35):4427-38. doi: 10.1200/JCO.2012.42.7161. Epub 2012 Sep 17.
- Background: PubMed 12203164Santolaya ME, Alvarez AM, Aviles CL, Becker A, Cofre J, Enriquez N, O'Ryan M, Paya E, Salgado C, Silva P, Tordecilla J, Varas M, Villarroel M, Viviani T, Zubieta M. Prospective evaluation of a model of prediction of invasive bacterial infection risk among children with cancer, fever, and neutropenia. Clin Infect Dis. 2002 Sep 15;35(6):678-83. doi: 10.1086/342064. Epub 2002 Aug 23.
- Background: PubMed 19996816Hakim H, Flynn PM, Srivastava DK, Knapp KM, Li C, Okuma J, Gaur AH. Risk prediction in pediatric cancer patients with fever and neutropenia. Pediatr Infect Dis J. 2010 Jan;29(1):53-9. doi: 10.1097/INF.0b013e3181c3f6f0.
- Background: PubMed 24105485Vidal L, Ben Dor I, Paul M, Eliakim-Raz N, Pokroy E, Soares-Weiser K, Leibovici L. Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients. Cochrane Database Syst Rev. 2013 Oct 9;2013(10):CD003992. doi: 10.1002/14651858.CD003992.pub3.
- BackgroundZapata-Tarrés Marta, Klünder-Klünder Miguel, Cicero-Oneto Carlo, Rivera-Luna Roberto, Ortega-Ríos Velasco Fernando, Cortés Gallo Gabriel et al . Análisis de la atención de las complicaciones durante el tratamiento de niños con leucemia linfoblástica aguda. Bol. Med. Hosp. Infant. Mex.
- Background: PubMed 25234044Aviles-Robles M, Ojha RP, Gonzalez M, Ojeda-Diezbarroso K, Dorantes-Acosta E, Jackson BE, Johnson KM, Caniza MA. Bloodstream infections and inpatient length of stay among pediatric cancer patients with febrile neutropenia in Mexico City. Am J Infect Control. 2014 Nov;42(11):1235-7. doi: 10.1016/j.ajic.2014.07.021. Epub 2014 Sep 16.
- Derived from this study: PubMed 32196898Aviles-Robles MJ, Reyes-Lopez A, Otero-Mendoza FJ, Valencia-Garin AU, Penaloza-Gonzalez JG, Rosales-Uribe RE, Munoz-Hernandez O, Garduno-Espinosa J, Juarez-Villegas L, Zapata-Tarres M. Safety and efficacy of step-down to oral outpatient treatment versus inpatient antimicrobial treatment in pediatric cancer patients with febrile neutropenia: A noninferiority multicenter randomized clinical trial. Pediatr Blood Cancer. 2020 Jun;67(6):e28251. doi: 10.1002/pbc.28251. Epub 2020 Mar 20.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martha J. Aviles Robles principal investigator
Hospital Infantil de Mexico Federico Gomez
Questions about this trial
What is this clinical trial studying?
A study testing Outpatient oral treatment. and Inpatient intravenous treatment. in people with Chemotherapy-Induced Febrile Neutropenia, run by Hospital Infantil de Mexico Federico Gomez.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Therapeutic failure as unfavorable clinical outcome of children with fever and neutropenia treated with oral outpatient antibiotic. (time frame: 17 days after randomization.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04000711, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2019.